One thing that I have believed is that the future will/should belong to more combination therapies for a lot of targets hit by small molecules. The last project I worked on almost certainly required a combination drug to have efficacy; or we needed a compound that could hit two or more biological receptors in the same class-something very difficult or impossible to achieve with high enough activity against all targets. I imagine we are going to discover many more cases like this as we learn more about the human genome and it's biology.
Combination therapies have been developed in the past (see AIDs drugs or cancer treatments, for example- and doctors and researchers have created ad hoc combinations for decades out of the known pharmacopeia), but they typically are combinations of already approved drugs that have efficacy independent of each other. In the case of my project, it is almost certain that the lead compound will fail in the clinical trials due to a lack efficacy, as has happened at other companies targeting the same receptor or receptors in the same class. If you were going to develop a combination therapy of two NMEs, you must put each compound through the clinic separately, get them approved, and then do the clinical trials again on the combination. And the FDA might deny approval in the individual cases because of a lack of efficacy- a sort of Catch 22.
One other thing I would recommend as a reform has to do with the patent law. It is getting increasingly difficult to patent small molecules because their structures are increasingly found in the ever growing patent literature for completely different targets. I know for a fact that a lot of projects begin on a less than optimal structure for reasons of patentability alone.
I understand why companies act this way--it gives them the most flexibility in going after their target. But it puts a lot of good molecules in limbo. Once a molecule is patented, the clock starts ticking towards the expiration date of the patent. And once the molecule is close to, or beyond that expiration date, there's no point in a company going after it, because a generic drug will virtually never earn back the R&D money sunk into bringing it through clinical trials.
Ultimately, this is a problem for the government to solve; it's a problem created by the rules that could be fixed, or at least mitigated, by rule changes. I can think of several different ways you could accomplish this:
- Have the FDA pay for clinical trials of drugs that are in the public domain
- Allow shorter term "repatents" of molecules that have never been approved as NMEs--by any company that gets them through clinical trials.
- Tighten up on what you allow to be patented
- Offer prizes for novel and effective uses for off-patent molecules
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